ABSORB III and IV Trials Aim to Prove Superiority of BVS

San Francisco, CA—Bioresorbable vascular scaffolds, when compared with everolimus-eluting stents, are showing promising results in preliminary clinical trials.

Stephen G. Ellis, MD, of the Cleveland Clinic, presented data on the ABSORB III trial that is underway and is designed to support the US post-market approval of BVS (Absorb, Abbott Vascular). Data from the serial quantitative IVUS study in ABSORB cohort B indicate a lessening of total plaque area between 12 and 36 months.

“This would not be seen with a traditional metal stent,” Ellis said.

TCT course director Gregg W. Stone, MD, of Columbia University Medical Center, presented data on the ABSORB IV trial, designed to evaluate clinical superiority of BVS compared with EES (Xience, Abbott Vascular). The trial is assessing reductions in late adverse events after PCI.

“If we can reduce angina in our patients, then BVS will truly be the next revolution in interventional cardiology,” Stone said.

ABSORB III

In the trial, up to 2,250 patients at 220 US and non-US sites will be enrolled; the primary endpoint is 1-year target lesion failure powered for noninferiority. Reference vessel diameters range from 2.5 mm to 3.75 mm with a lesion length ≤24 mm.

The primary objective of the 2:1 trial is to evaluate the safety and effectiveness of the Absorb BVS System compared with EES in the treatment of subjects with ischemic heart disease caused by up to two de novo native coronary artery lesions in separate epicardial vessels. The BVS system elutes everolimus in a similar way to Xience V (Abbott Vascular) and then resorbs naturally into the body, leaving no permanent scaffold. There is a gradual loss of structural integrity with the scaffold starting around 12 to 24 months with total dissolution of the scaffold by 36 to 42 months, which allows the return of vasomotion.

“It’s notable to point out that the Xience family of stents can be utilized in the control arm: Xience V, Xience Xpedition or Xience Prime,” Ellis said.

Potential for the unique benefits of Absorb, such as late lumen gain and enhanced vasomotion, have been observed in earlier clinical studies and will be further evaluated in ABSORB III, Ellis said.

ABSORB IV

Stone discussed the trial characteristics for ABSORB IV, which is the second part of the ABSORB III clinical trial program that will include an additional 3,000 patients randomized 1:1 with Xience.

The primary endpoint is patient-reported angina at the end of 1 year and a reduction in target lesion failure between 1 and 5 years.

While DES are effective, there remain two outstanding issues after PCI – recurrent angina and accrual of very late adverse events, he said. Based on the SPIRIT IV trial results, Stone said target lesion-related events occur at a rate of about 2.6% per year, long after the restenosis process is considered supposedly complete. Potential causes for very late thrombosis include uncovered stent struts; abnormal shear stress from protruding struts and/or loss of cyclic strain relief (compliance mismatch); chronic inflammation due to late foreign body reactions and polymer hypersensitivity; positive remodeling with strut malapposition; strut fracture; and neoatherosclerosis.

“These don’t only happen with DES, they happen with BMSs, too,” Stone said. “Putting a metal cage in a vessel leads to ongoing late events.”

Incidence of angina recurrence at 1 year after PCI is high, as proven by several studies, including FREEDOM, 10 MVD, SPIRIT IV, SYNTAX and COURAGE. Data from a propensity-matched analysis (EXTEND vs. SPIRIT IV, unpublished data) showed that over time, patients with Absorb (16%) reported less angina than patients with Xience (28%) (P=0001). Stone said the potential for fewer instances of angina and ischemia with Absorb could stem from expansion of the internal elastic membrane and growth of the lumen as the device begins to dissolve and the vessel is constrained.

BVS may also reduce the incidence of late events because it could allow for restoration of normal vasomotion, normal shear stress and cyclic strain; normal vessel curvature; reduced risk of very late polymer reactions; avoidance/resolution of positive remodeling and stent malapposition; avoidance/resolution of late strut fractures; less neoatherosclerosis; less plaque regression; and less angina.

Disclosures:

Ellis received consultant fees from Abbott Vascular, Boston Scientific and Medtronic CardioVascular.

Stone received consultant fees from Boston Scientific and REVA.